Cell-perceived substrate curvature dynamically coordinates the direction, speed, and persistence of stromal cell migration

Adherent cells residing within tissues or biomaterials are presented with 3D geometrical cues from their environment, often in the form of local surface curvatures. While there is growing evidence that cellular decision‐making is influenced by substrate curvature, the effect of physiologically relevant, cell‐scale anisotropic curvatures remains poorly understood. This study systematically explores the migration behavior of human bone marrow stromal cells (hBMSCs) on a library of anisotropic curved structures. Analysis of cell trajectories reveals that, on convex cylindrical structures, hBMSC migration speed and persistence are strongly governed by the cellular orientation on the curved structure, while migration on concave cylindrical structures is characterized by fast but non‐aligned and non‐persistent migration. Concurrent presentation of concave and convex substrates on toroidal structures induces migration in the direction where hBMSCs can most effectively avoid cell bending. These distinct migration behaviors are found to be universally explained by the cell‐perceived substrate curvature, which on anisotropic curved structures is dependent on both the temporally varying cell orientation and the 3D cellular morphology. This work demonstrates that cell migration is dynamically guided by the perceived curvature of the underlying substrate, providing an important biomaterial design parameter for instructing cell migration in tissue engineering and regenerative medicine.